Mesenchymal Stem Cells Restore Endometrial Integrity and Sustain Pregnancy via CCR7‐ERK/JNK Signaling Modulation
Yunguo Lei, Juanmei Gao, Ning Zhang, Yunjun Lin, Weihua Yang, Yuequn Chen, Qiang Wei, Jianmei Xia
TL;DR
Mesenchymal stem cells help repair the endometrium and support pregnancy by modulating immune cells and signaling pathways in a rat model of recurrent pregnancy loss.
Contribution
The study identifies the CCR7-ERK/JNK signaling axis as a novel therapeutic target for idiopathic recurrent pregnancy loss using mesenchymal stem cells.
Findings
MSC treatment increased embryo retention by 190% in a rat model of RPL.
MSCs upregulated CCR7 and activated NK differentiation pathways in NK92 cells.
MSCs modulated cytokine profiles by reducing pro-inflammatory markers and increasing IL-10.
Abstract
Recurrent pregnancy loss (RPL), defined as more than two consecutive miscarriages before 20 weeks of gestation, affects 1%–5% of reproductive‐aged women, with nearly half of the cases remaining idiopathic. Using ethanol‐induced endometrial injury in rats to simulate RPL, we demonstrated that mesenchymal stem cells (MSCs) exert therapeutic effects through two complementary mechanisms: CCR7‐mediated endometrial repair and immunomodulation of uterine natural killer (uNK) cells, compared to ethanol‐induced injury, this treatment achieved a 190% increase in embryo retention (from 2.4 to 7 embryos). Transcriptomic analysis and Western blotting of MSC‐cocultured NK92 cells revealed significant CCR7 upregulation (1.75‐fold increase at the optimal dose of 2 × 104 cells/mL MSCs) and activation of NK differentiation pathways. This was corroborated by immunofluorescence showing enhanced CCR7+ NK…
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Taxonomy
TopicsReproductive System and Pregnancy · Endometriosis Research and Treatment · Mesenchymal stem cell research